Novel Experimental and Clinical Therapeutic Uses of Low-Molecular-Weight Heparin/Protamine Microparticles

Kishimoto, Satoko; Takikawa, Megumi; Mori, Yasutaka; Hattori, Hidemi; Fujita, Masanori; Nakamura, Shingo

doi:10.3390/pharmaceutics4010042

Cited by 9 publications

(5 citation statements)

References 54 publications

(99 reference statements)

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“…Basic molecules such as chitosan and protamine are typically complexed (through ionic interactions) with acidic molecules such as mucopolysaccharides, alginate, and fucoidan; the resulting assemblies are termed polyelectrolyte complexes (PECs) [ 38 , 68 , 69 , 70 ]. Studies indicate that polyanions and polycations can bind to proteins below and above their isoelectric points, respectively.…”

Section: Structure Of the Gi Mucosa And Formation Of Polyelectrolymentioning

confidence: 99%

Development of Mucoadhesive Chitosan Derivatives for Use as Submucosal Injections

Hattori

2018

Polymers

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Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been used for surgical treatment of early gastric cancer. These endoscopic techniques require proper submucosal injections beneath the tumor to provide a sufficiently high submucosal fluid cushion (SFC) to facilitate clean dissection and resection of the tumor. Until now, the submucosal injection materials developed for endoscopic techniques such as EMR and ESD of tumors have been composed of macromolecules, proteins, or polysaccharides. We have been investigating the use of chitosan, a product that is obtained by the alkaline deacetylation of chitin, the second-most abundant natural polysaccharide. Specifically, we have been studying a photocrosslinked chitosan hydrogel (PCH) and solubilized chitosan derivatives for use as novel submucosal injections for endoscopic techniques. Notably, chitosan derivatives with lactose moieties linked to the amino groups of its glucosamine units can specifically interact with acidic mucopolysaccharides and mucins in submucosa without the need for the incorporation of harmful photoreactive groups nor potentially mutagenic ultraviolet irradiation.

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Section: Structure Of the Gi Mucosa And Formation Of Polyelectrolymentioning

confidence: 99%

Development of Mucoadhesive Chitosan Derivatives for Use as Submucosal Injections

Hattori

2018

Polymers

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“…, hematopoietic cells (HCs) and BMSCs. The BMSCs and ADSCs are multipotential, indicating that in culture [ 1 , 2 , 3 ] or after in vivo implantation these cells can differentiate into a variety of cell types including osteoblasts, chondrocytes and adipocytes etc.…”

Section: Biomedical Applications Of Low Molecular Weight Heparin/pmentioning

confidence: 99%

“…Basic protamine molecules complexed with acidic molecules such as heparin form complexes through ionic interactions [ 2 ]. We previously have reported the low molecular weight heparin/protamine nano/micro particles (LMWH/P N/MPs), which we originally prepared as polyelectrolyte complexes (PECs) [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix

Kishimoto

Takikawa

Hattori

et al. 2015

IJMS

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Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields a dispersion of N/MPs (100 nm–3 μm in diameter). LMWH/P N/MPs can be immobilized onto cell surfaces or extracellular matrix, control the release, activate GFs and protect various GFs. Furthermore, LMWH/P N/MPs can also bind to adhesive cell surfaces, inducing cells and LMWH/P N/MPs-aggregate formation. Those aggregates substantially promoted cellular viability, and induced vascularization and fibrous tissue formation in vivo. The LMWH/P N/MPs, in combination with ADSCs or BMSCs, are effective cell-carriers and are potential promising novel therapeutic agents for inducing vascularization and fibrous tissue formation in ischemic disease by transplantation of the ADSCs and LMWH/P N/MPs-aggregates. LMWH/P N/MPs can also bind to tissue culture plates and adsorb exogenous GFs or GFs from those cells. The LMWH/P N/MPs-coated matrix in the presence of GFs may provide novel biomaterials that can control cellular activity such as growth and differentiation. Furthermore, three-dimensional (3D) cultures of cells including ADSCs and BMSCs using plasma-medium gel with LMWH/P N/MPs exhibited efficient cell proliferation. Thus, LMWH/P N/MPs are an adequate carrier both for GFs and for stromal cells such as ADSCs and BMSCs, and are a functional coating matrix for their cultures.

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“…Studies have explored the in vitro coassembly of heparin and protamine and demonstrated their coassembly into nanometer- or micrometer-sized particles that are useful for biomedical applications [ 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. For particle preparation, low-molecular-weight heparin (several kDa), which is fractionated from heparin (10–20 kDa), is frequently used instead of heparin due to the lower risk of bleeding with the low-molecular-weight form [ 25 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Recent Progress on Heparin–Protamine Particles for Biomedical Application

2022

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Biomolecules are attractive building blocks with self-assembly ability, structural diversity, and excellent functionality for creating artificial materials. Heparin and protamine, a clinically relevant pair of biomolecules used in cardiac and vascular surgery, have been shown to coassemble into particulate polyelectrolyte complexes in vitro. The resulting heparin–protamine particles exhibit adhesive properties that enable advantageous interactions with proteins, cells, and various other substances and have been employed as functional materials for biomedical applications. In this review article, we summarize recent progress in research on the use of heparin–protamine particles as drug carriers, cell adhesives, and cell labels. Studies have demonstrated that heparin–protamine particles are potentially versatile in biomedical fields from drug delivery and regenerative medicine to plastic surgery.

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Novel Experimental and Clinical Therapeutic Uses of Low-Molecular-Weight Heparin/Protamine Microparticles

Cited by 9 publications

References 54 publications

Development of Mucoadhesive Chitosan Derivatives for Use as Submucosal Injections

Development of Mucoadhesive Chitosan Derivatives for Use as Submucosal Injections

Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix

Recent Progress on Heparin–Protamine Particles for Biomedical Application

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